Rd. Mcbane et al., ANTITHROMBOTIC ACTION OF ENDOGENOUS PORCINE PROTEIN-C ACTIVATED WITH A LATENT PORCINE THROMBIN PREPARATION, Thrombosis and haemostasis, 74(3), 1995, pp. 879-885
Endogenously activated protein C is evaluated for antithrombotic activ
ity in porcine carotid arteries subjected to mechanical trauma. Protei
n C is activated by intravenous administration of guanidinobenzoyl-thr
ombin, which binds to thrombomodulin and there deacylates to yield thr
ombin. The bound, transiently active thrombin yields a peak of anticoa
gulant activity between 5 and 10 min after infusion of the latent thro
mbin. Inhibition of thrombin binding in vivo by co-infusing an active-
site-blocked thrombin preparation elicits acute and lethal systemic th
rombosis. Nearly occlusive platelet thrombosis, which occurs within 30
min of crushing 1 cm segments of carotid arteries with a standard hem
ostat, is blocked by endogenous protein C activation initiated 2 min b
efore the crush injury. It is concluded that activated protein C block
s thrombosis in deeply injured musculo-elastic arteries, and that acti
vation of latent thrombin bound to thrombomodulin in vivo is a practic
al means for delivery of pharmacologically effective concentrations of
activated protein C.